Background: Cassia obtusifolia is a traditional Chinese medicine used in lowering blood lipids, but the specific compounds and mechanisms responsible for this action are still unknown. Anthraquinones are the primary active components of C. obtusifolia, among which 1,8-dihydroxyanthraquinone (DHAQ) exhibits strong biological activities. Aim: The effects of DHAQ on blood lipids and the underlying mechanisms were investigated in this study to provide a reliable experimental basis for the development and application of C. obtusifolia. Materials and Methods: Mice were fed with a high-fat diet for the establishment of a hyperlipidemia mouse model. After the establishment of the model, the mice were intragastrically administered with 5 mg/kg DHAQ once daily, continuously for 6 weeks. Then, the mice were weighed; their lipid/body ratios were calculated; their serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured. TG and TC contents in the liver tissue samples were measured by the enzyme-linked immunosorbent assay. Reverse transcription–polymerase chain reaction was performed to detect the levels of 7α-hydroxylase (CYP7A1) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) mRNA, and Western blot analysis was performed to detect the expression levels of HMGCR and CYP7A1 proteins in the liver tissue of mice. Results: Body weights and lipid/body ratios of the hyperlipidemic mice were significantly reduced, and the levels of TG, TC, and LDL-C were significantly reduced in the serum samples. However, the HDL-C content in the serum was significantly increased, and TG and TC contents in the liver tissue were significantly reduced in the DHAQ-treated hyperlipidemic mice. In addition, the expression of CYP7A1 and HMGCR proteins was respectively increased and decreased significantly in the liver tissue of the hyperlipidemic mice. Conclusion: DHAQ revealed a hypolipidemic effect in hyperlipidemia mice fed on a high-fat diet, which may be related to the regulation of cholesterol metabolism in the liver.